Significant Unresolved Questions and Opportunities for Bioengineering in Understanding and Treating COVID-19 Disease Pro
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Cellular and Molecular Bioengineering ( 2020) https://doi.org/10.1007/s12195-020-00637-w
COVID-19
Significant Unresolved Questions and Opportunities for Bioengineering in Understanding and Treating COVID-19 Disease Progression JASMINE SHIRAZI,1 MICHAEL J. DONZANTI,1 KATHERINE M. NELSON,2 RYAN ZURAKOWSKI,1 CATHERINE A. FROMEN,2 and JASON P. GLEGHORN 1 1
Department of Biomedical Engineering, University of Delaware, 161 Colburn Lab, Newark, DE 19716, USA; and 2Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE 19716, USA (Received 29 May 2020; accepted 14 July 2020) Associate Editor Owen McCarty oversaw the review of this article.
Abstract—COVID-19 is a disease that manifests itself in a multitude of ways across a wide range of tissues. Many factors are involved, and though impressive strides have been made in studying this novel disease in a very short time, there is still a great deal that is unknown about how the virus functions. Clinical data has been crucial for providing information on COVID-19 progression and determining risk factors. However, the mechanisms leading to the multi-tissue pathology are yet to be fully established. Although insights from SARS-CoV-1 and MERS-CoV have been valuable, it is clear that SARS-CoV-2 is different and merits its own extensive studies. In this review, we highlight unresolved questions surrounding this virus including the temporal immune dynamics, infection of non-pulmonary tissue, early life exposure, and the role of circadian rhythms. Risk factors such as sex and exposure to pollutants are also explored followed by a discussion of ways in which bioengineering approaches can be employed to help understand COVID-19. The use of sophisticated in vitro models can be employed to interrogate intercellular interactions and also to tease apart effects of the virus itself from the resulting immune response. Additionally, spatiotemporal information can be gleaned from these models to learn more about the dynamics of the virus and COVID-19 progression. Application of advanced tissue and organ system models into COVID-19 research can result in more nuanced insight into the mechanisms underlying this condition and elucidate strategies to combat its effects. Keywords—COVID-19, ACE2, Circadian rhythms, Organotypic models, Placenta, Cytokine storm, ARDS, Host response, Immune, Sex differences.
Address correspondence to Jason P. Gleghorn, Department of Biomedical Engineering, University of Delaware, 161 Colburn Lab, Newark, DE 19716, USA. Electronic mail: [email protected]
INTRODUCTION As SARS-CoV-2 (the virus) infection continues to spread worldwide, the scientific community is working to characterize the pathophysiology of COVID-19 (the disease) in the hopes of developing effective therapeutics to ease the burden being caused by this pandemic. Whereas insights from SARS-CoV-1 and MERS-CoV have been helpful, it has become clear that SARSCoV-2 is more contagious and displays idiosyncrasies that separate it from the other zoonotic coronaviruses.33 Impre
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